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Biomedical subjects

R Ziegler

Publications and source records attributed to R Ziegler.

At least 487 records · Page 27Linked to original sources

Synthetic human calcitonin (Cibacalcin, Ciba-Geigy): use for radioimmunoassay and bioassay.

Two batches of synthetic human calcitonin batch A = delivered until 1976, and batch B = distributed since 1977 from Ciba-Geigy, have been tested and compared biologically and radioimmunologically. In the biossay B is almost twice as active as A when compared ampoule content and exerts a biological activity of 188 IU per mg pure hCT. In the radioimmunoassay there is no difference from each other in radioiodination and purification, but using them as standard and again comparing them on declared ampoule content, B contains twice as much immunological activity as A. For those, who are using hCT for analytic or biological purposes it is of importance to consider the increased hormone content of batch B with a twofold biological and immunological activity, in comparison to the preparations delivered before 1977.

Animals↗

Trapping of metabolically generated electrophilic species with cyanide ion: metabolism of methapyrilene.

The popular antihistamine methapyrilene [N,N-dimethyl-N'-(2-pyridyl)-N'-(2-thienylmethyl)-1,2-ethanediamine] recently has been shown to be a potent hepatocarcinogen. Metabolic studies with rabbit liver 100000g microsomal preparations have resulted in the partial characterization of the in vitro metabolic profile of methapyrilene. Evidence for the formation of the N-oxide and the three possible carbinolamines resulting from the NADPH-dependent oxidation of the (dimethylamino)ethyl side chain nitrogen and carbon atoms of methapyrilene is presented. Attempts to trap iminium ion intermediates with electrophilic alkylating potential by coincubating methapyrilene with sodium cyanide have led to the isolation of N-(cyanomethyl)normethapyrilene. The possibility of characterizing the iminium ion intermediate that would result from the oxidative deamination of the dimethylamino moiety was precluded by the chemical instability of the corresponding alpha-cyano amine, which undergoes a spontaneous retro-Michael reaction and hydrolysis to the corresponding amide. The results are discussed in terms of the metabolic activation of methapyrilene to potential alkylating species.

Aminopyridines↗

[X-ray examination of the shoulder in suspected luxation (author's transl)].

The X-ray examination of an injured part of a skeleton requires, to obtain a 3-D effect, two vertical levels to one another. The explanation of this radiographic minimum demand is seen especially in the posterior dislocation of the shoulder as the a-p-view with the discrete indirect signs of luxation; this is often misinterpreted as being normal by inexperienced people. Indirect X-ray signs are: fixed internal rotation of the Humerus, "Trough-line", positive "Rim-sign", flattening of the medial aspect of the humeral head and "loss of the normal half-moon shadow" caused by the overlap of the humeral head on the posterior part of the glenoid cavity. The position of the second dimension is brought out with more success using the transscapular or the Velpeau axillary view radiogram without in being painful for the patient.

Diagnosis, Differential↗

Di- and tri-methoxystyryl derivatives of heterocyclic nitrogen compounds.

A series of mono-, di-, and trimethoxystyryl derivatives of heterocyclic nitrogen compounds were prepared to test the N-O-O triangulation hypothesis of Zee-Cheng and Cheng. Of 29 free bases submitted for KB cell culture test, only 2-(3,4-methylenedioxystyryl)benzoxazole and 4-(2,5-dimethoxystyryl)cinnoline were active (ED50 of 4 microgram/ml or less). Methiodide salts were more potent: 8 of 14 were active. 2-(2,4,6-Trimethoxystyryl)quinoline methiodide and 4-(2,4,5-trimethoxystyryl)quinoline methiodide had ED50 of 0.4 and 0.9 microgram/ml, respectively. The methiodides of 2-(2,3,4-, 4-(2,4,5-, 4-(2,4,6-, and 2,4-bis-(2,4,6-trimethoxystyryl)quinoline and 1-(2,4,6-trimethoxystyryl) isoquinoline and the propiodide of 4-(2,4,6-trimethoxystyryl)quinoline were active against P388 leukemia. Several of the active compounds do not conform to the dimensions of the Zee-Cheng and Cheng triangle.

Animals↗

[Renal osteodystrophy in children. Therapy with 1,25-dihydroxy-cholechalciferol (author's transl)].

Growth arrest and renal osteodystrophy are major problems in renal insufficiency of children. The present report describes our experiences in managing renal osteodystrophy in 14 dialyzed children using 1,25-DHCC for 12 months. Values in plasma of Ca, P, Mg, alkaline phosphatase, iPTH, 25-OH-D, and 1,25-DHCC were determined regulary. Skeletal X-rays and analysis of iliac crest biopsies were obtained in each child. In treatment with 1,25-DHCC episodes of severe but reversible hypercalcemia occurred. Alkaline phosphatase and iPTH normalized completely. Radiographic examinations revealed marked improvement. Histological signs of fibro-osteoclasia and resorptive defects disappeared but there was no recovery of osteomalacia. A reduction of osteoblast population and of bone transformation was obvious. 1,25-DHCC failed to normalize growth in uremic children. In short, neither vitamin D nor 1,25-DHCC can guarantee complete recovery of renal osteodystrophy and growth arrest in uremic children.

Adolescent↗

Parathyroid function and serum calcitonin in children receiving anticonvulsant drugs.

Serum calcitonin (CT) levels and other aspects of calcium metabolism were investigated in 40 epileptic children receiving long-term treatment with phenytoin and/or other anticonvulsant drugs, and in 38 age-matched controls. In the patients CT levels were significantly lower. Immunoreactive parathyroid hormone (iPTH) was significantly elevated exceeding the upper limit of controls in 11 patients. We also observed a highly significant correlation between iPTH and urinary cyclic AMP (cAMP) excretion but a lack of such a correlation with the renal handling of phosphate; this indicates to us a dissociation between cAMP production and phosphaturia. A significant correlation between iPTH levels and urinary hydroxyproline excretion points to a normal action of PTH on bone in the patients. The low CT levels are not due to hypocalcemia and may be directly attributed to the effects of anticonvulsant drugs. As the primary effect of CT is a direct inhibition of PTH induced calcium loss from bone, the drug-related low CT levels in association with secondary hyperparathyroidism possibly is an additional factor in anticonvulsant bone disease.

Adolescent↗

Inhibition of human gastric secretion by intragastrically administered calcitonin.

The effects of intragastrically administered synthetic human calcitonin (H-CT) and salmon calcitonin (S-CT) on human gastric secretion have been compared with the effects of both CTs after intravenous infusion. Basal as well as pentagastrin-stimulated acid and pepsin output were lowered by about 50% in response to a single intragastric instillation of H-CT while an intravenous infusion of H-CT produced an inhibition of more than 70%. After intragastric instillation, dose-response curves of H-CT and S-CT were in a similar range when the dose was referred to the molarity of CT; however, related to the biological activity of CT (MRC units), S-CT was about 10--15 times less effective than H-CT. Conversely, after intravenous infusion, equal doses in reference to MRC units evoked similar responses while in reference to molarity S-CT was 20--30 times more effective than H-CT. Radioimmunological determinations of H-CT showed after intragastric instillation a stepwise decrease in concentration of H-CT in the gastric juice and no appearance of H-CT in the blood. In contrast, after intravenous administration of H-CT, no detectable H-CT activity was secreted into the juice in the presence of a peak increase in serum-immunoreactive H-CT. From the differences in the effects of CT observed after intragastric and intravenous administration, respectively, it is suggested that intragastrically administered CT might inhibit gastric secretion via local mechanisms on the gastric mucosa.

Adult↗

Calciotropic hormones and lipolysis of human adipose tissue: role of extracellular calcium as conditioning but not regulating factor.

The influences of different calcium concentrations (0, 0.924 and 2.772 mMol/l) on lipolysis of in vitro incubated human adipose tissue slices or adipocytes were studied under the conditions of stimulation with isoproterenol and parathyroid hormone preparations or inhibition by insulin. Extractive bovine PTH (as well as synthetic PTH 1--34) stimulated glycerol release in a biphasic pattern similarly to isoproterenol; PTH was about half as potent as isoproterenol. The optimal conditions for lipolysis were observed using a calcium concentration of 0.924 mMol/l, whereas lipolysis was distinctly impaired at concentrations of 0 or 2.772 mMol/l; this was true for basal as well as isoproterenol- and PTH stimulated lipolysis or the inhibitory effect of insulin. In contrast to partially purified extractive calcitonin, pure synthetic calcitonin did not inhibit lipolysis. Isoproterenol- and PTH-administrations led to cAMP accumulation in the adipose tissue, this process was also diminished at the non-optimal calcium concentrations. The results suggest a conditioning, but not a regulating significance of extracellular calcium for lipolysis, whereas the importance of the lipolytic potency of PTH remains to be elucidated.

Adipose Tissue↗

[On the question of endocrine side effects in patients on medication for renal calcium stone disease (author's transl)].

In patients with recurrent idiopathic nephrolithiasis we studied whether treatment with sodium cellulose phosphate leading to decreased intestinal calcium absorption could induce secondary hyperparathyroidism and whether thiazides which diminish calciuria would impair glucose tolerance. After removal of a actual kidney stone, 74 patients were treated for one year as follows: 25 (group 1) received conventional therapy (Nieron), 22 (group 2) received sodium cellulose phosphate, and 27 (group 3) received sodium cellulose phosphate plus hydrochlorothiazide. The period of one year was too short to evaluate the effectiveness of treatment regarding stone recurrence, however, a significant decrease in calciuria only was seen in group 3. With respect to the possibility to develop secondary hyperparathyroidism, group 2 and group 3 did not reveal any hints. In group 3, the thiazide treatment did not worsen glucose tolerance. Therefore, longer lasting studies with these drugs could be performed without evident danger to develop the mentioned side effects.

Calcium↗

[Improvement of growth-hormone stimulation with l-dopa/l-carbidopa by simultaneous administration of propranolol (author's transl)].

The effect of simultaneous administration of 250 mg L-dopa + 25 mg L-carbidopa (Nacom) and 1 mg propranolol/kg body weight (maximal dose 40 mg propranolol) on growth-hormone secretion was tested in 96 children with growth retardation. The results were compared with those in a group of children that had been receiving only L-dopa and L-carbidopa. The additional administration of propranolol reduced the number of children unresponsive to adequate growth-hormone stimulation from 16% to 9.5%. There was no significant difference in mean maximal growth-hormone level between both groups, but the addition of propranolol caused a more long-lasting rise in serum growth hormone levels. Some of the children who previously had failed to have a satisfactory rise in growth-hormone level after L-dopa and L-carbidopa showed satisfactory stimulation when propranolol was added. Since only three blood samples need be taken (0, 45 and 90 minutes) and no significant side effects were noted, the combined treatment is suitable for out-patient use.

Carbidopa↗